Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
2557448 Polyarticular Clostridium perfringens pyoarthritis. 1989 Nov A woman with rheumatoid arthritis presented with an abdominal mass and Clostridium perfringens septic arthritis in both wrists and shoulders. We believed this to be the first reported case of polyarticular septic arthritis due to Clostridium perfringens. Apatite, lipid, and cholesterol crystals in the shoulder joint effusions were a potential source of diagnostic confusion.
2888437 Histamine H1 receptors on adherent rheumatoid synovial cells in culture: demonstration by 1987 Jun Histamine H1 receptors have been demonstrated on adherent rheumatoid synovial cells using biochemical and radioligand binding assays in vitro. The addition of histamine (17.8 mumol/l) to nine primary cultures of adherent rheumatoid synovial cells resulted in a two- to 21-fold increase in the production of prostaglandin E (PGE). This increase was inhibited by three H1 receptor antagonists (mepyramine, tripelennamine, and chlorpheniramine) in a dose related manner at concentrations below 10(-6) mol/l. Competitive binding assays with [3H]mepyramine gave ED50 values of approximately 10(-5) mol/l for the three H1 antagonists. H2 receptor antagonists (cimetidine and ranitidine) did not inhibit the histamine induced increase in PGE and did not compete effectively with the binding of H1 antagonists.
2448638 Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. 1988 Jan 14 Adjuvant arthritis (AA) is a chronic disease inducible in rats by immunization with an antigen of Mycobacterium tuberculosis. After the isolation of arthritogenic T-cell lines and clones, it became possible to demonstrate that the critical M. tuberculosis antigen contained an epitope cross-reactive with a self-antigen in joint cartilage. Like AA rats, patients suffering from rheumatoid arthritis demonstrated specific T-lymphocyte reactivity to the M. tuberculosis fraction containing the cross-reactive epitope. To characterize the critical M. tuberculosis epitope we used AA T-cell clones to screen mycobacterial antigens expressed in Escherichia coli and genetically engineered truncated proteins and synthetic peptides. The AA T-cell clones recognized an epitope formed by the amino acids at positions 180-188 in the sequence of a Mycobacterium bovis BCG antigen. Administration of this antigen to rats induced resistance to subsequent attempts to produce AA.
1677345 [Modulation of immunocompetent cells in the synovial fluid TGF-beta]. 1991 Apr Mononuclear cells (MNC) in synovial fluids from patients with rheumatoid arthritis and other arthropathies differ clearly from MNC in peripheral blood. Typically the ratio of CD4(+)-/CD8+ lymphocytes is inverted and the response to mitogens/cytokines (IL-1/IL-2) is impaired. Active TGF-beta (transforming growth factor beta) was found to account for these abnormalities, and the major isoform was identified as TGF-beta 2.
3172099 Intravenous cyclophosphamide and methylprednisolone for the treatment of bronchiolitis obl 1988 A patient with rheumatoid arthritis receiving intramuscular gold developed severe pulmonary insufficiency. Histopathology revealed both bronchiolitis obliterans and interstitial fibrosis possibly related to gold therapy. The patient was successfully treated with IV cyclophosphamide and prednisone. During the course of therapy, hypogammaglobulinemia without detectable IgM developed.
1722494 Human group II phospholipase A2. Characterization of monoclonal antibodies and immunochemi 1991 Dec 15 Murine monoclonal and rabbit polyclonal antibodies were generated against human group II phospholipase A2 (PLA2) in order to study the role of this enzyme in inflammatory disease, the source of its synthesis, and the interaction of PLA2 with its substrate. Monoclonal antibody PLA187 exhibits potent inhibitory activity toward human PLA2 using autoclaved E. coli membranes as the substrate. Three other monoclonal antibodies (PLA184, PLA185, and PLA186) also inhibit enzyme activity, but with about 50-fold less potency. Based on the results of double-antibody competition experiments and enzyme inhibition profiles, PLA184 and PLA185 appear to recognize the same epitope. Monoclonal antibody PLA186 recognizes an epitope which is spatially distinct from that recognized by PLA184/185. The results also suggest that the epitope recognized by PLA187 may overlap with both epitopes recognized by PLA186 and PLA184/185. A double-antibody sandwich ELISA was developed using a combination of PLA185 and rabbit polyclonal antibody against PLA2. The ELISA provides a sensitive and quantitative method for monitoring specifically group II PLA2 in various biological sources, independent of factors which may affect enzyme activity. We have utilized this assay to quantitate PLA2 levels in synovial fluid from the joints of individuals with rheumatoid arthritis as well as from non-arthritic joints. Our results indicate that elevated levels of group II PLA2 in synovial fluid are not necessarily associated with arthritis.
1958090 Symptomatic salicylate ototoxicity: a useful indicator of serum salicylate concentration? 1991 Oct A three phase study was designed to define further the sensitivity and specificity of symptomatic salicylate ototoxicity (primarily tinnitus) for serum salicylate concentrations. In phase one 260 patients with osteoarthritis and 112 with rheumatoid arthritis, none taking salicylates, were interviewed about their ear symptoms. Their responses were not significantly different from those of 134 salicylate treated patients with rheumatoid arthritis previously reported. In the second phase 56 patients who were taking salicylates, and who volunteered the complaint of tinnitus, had serum salicylate concentrations measured while symptomatic, and 30 (54%) had concentrations less than 1.3 mmol/l. Few tolerated an upward salicylate dose adjustment. For phase three, 94 patients were found to have a salicylate concentration above 2.2 mmol/l on one or more occasion, and these subjects were interviewed. Fifty two patients (55%) had no tinnitus, and tinnitus correlated with the blood salicylate concentration in only 28 (30%). Audiological evaluation of most of the symptomatic patients was carried out, and results were abnormal in the majority, even in those patients not reporting tinnitus. Symptomatic salicylate ototoxicity is too nonspecific and too insensitive to be a useful indicator of serum salicylate concentration.
2602914 Rheumatoid synovial fluid reconstitutes the B-cell defect in CBA/N mice. 1989 Dec Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains a biological activity which can replace T cells for activation of antibody secretion in human blood lymphoid cells and which can also induce the selective differentiation of IgG2b-secreting cells in lipopolysaccharide (LPS)-pre-activated mouse spleen cells. The B-cell activity of this factor was studied in CBA/N mice which have an X-linked B-cell immunodeficiency which manifests itself as a defective humoral response to certain thymus-independent antigens (TI-2). RA-SF has now been shown to reconstitute partly the B-cell deficiency in CBA/N splenic B cells in vitro. Addition of RA-SF to LPS-pretreated cell cultures results in IgG2b secretion in CBA/N spleen cells as well. In contrast to cells from normal CBA mice, cells from CBA/N mice cannot respond to interleukin 4 (IL-4) after addition of LPS with production of IgG1 antibodies in vitro. However, the addition of RA-SF completely restores a normal IL-4-induced IgG1 response. No other biologically active factors have been shown to allow the production of IgG antibody producing cells in CBA/N splenic B cells. It is postulated that the xid immunodeficiency could be the result of a deficient production of a biological activity which is abundant in RA-SF.
2901303 Sulphasalazine in rheumatoid arthritis: combination therapy with D-penicillamine or sodium 1988 Jun This open study examined the safety of adding a second slow-acting anti-rheumatic drug (SARD) - D-penicillamine or sodium aurothiomalate - to the therapy of 38 rheumatoid patients already established on sulphasalazine. Combined anti-rheumatic therapy given in this way was generally well-tolerated and the incidence of adverse reactions was not increased. During the first year none of the reactions were serious although 9 of the 29 patients (31%) given D-penicillamine and 3 of the 9 patients receiving aurothiomalate developed side-effects requiring withdrawal of the second SARD. Reactions attributed to D-penicillamine were: gastro-intestinal - 6, rashes - 2, and blurring of vision - 1. All 3 reactions occurring with gold were rashes, 2 associated with proteinuria and one with increased liver enzymes. During the second year D-penicillamine was withdrawn in 4 patients due to thrombocytopenia - 2, and rashes - 2. In addition an overall favourable clinical response was achieved in 70% of patients. This approach for combination therapy whereby a second SARD is given to patients already established on a single SARD, appears to minimise the toxicity which is a problem when 2 SARDs are started simultaneously.
3264698 Outcome of pregnancy in patients with autoimmune rheumatic disease before the disease onse 1988 Dec The outcomes of 419 pregnancies of 154 unselected patients with various auto-immune diseases, including 390 pregnancies before the disease onset, were studied retrospectively. The patients comprised 40 with systemic lupus erythematosus (SLE), 72 with rheumatoid arthritis, 21 with primary Sjögren's syndrome (1 degree SS), 14 with progressive systemic sclerosis (PSS), and seven with mixed connective tissue disease. The histories of 267 pregnancies of 98 healthy, age matched women served as controls. Our data indicate that compared with healthy controls autoimmune patients do not experience a higher incidence of fetal loss. The incidence of fetal loss before disease onset in the various groups of autoimmune patients (as well as after disease onset in patients with SLE and RA) was not significantly different from that of controls. Spontaneous abortions in patients with 1 degree SS and PSS before disease onset occurred significantly more frequently (p less than 0.05) than in controls. Nevertheless, it should be noted that this was not the case when the incidence per woman was considered. On the other hand, patients with SLE, both before and after disease onset, experienced a higher incidence of premature deliveries (p less than 0.05). Finally, the analysis of autoantibody profiles, including antibodies to nuclear antigens, to Ro(SSA) cellular antigen, to double stranded DNA, and to cardiolipin, could not demonstrate any association of autoantibodies with any particular pregnancy outcome.
3031126 Antibodies against nuclear poly(A) polymerases in rheumatic autoimmune diseases. 1987 Jan Sera from 53 patients, 26 with systemic lupus erythematosus (SLE), 8 with rheumatoid arthritis (RA), 9 with Sjogren's syndrome (SS), and 10 with scleroderma (Scl), were screened for the presence of antibodies against liver-type poly(A) polymerase and tumor-type poly(A) polymerase. Sixty percent of the patients with the above four autoimmune diseases have antibodies directed against liver poly(A) polymerase, whereas sera from 74% of the patients contained anti-hepatoma poly(A) polymerase antibodies. About 25% of the patients produced antibodies exclusively against the tumor poly(A) polymerase. IgG containing anti-liver or anti-tumor poly(A) polymerase antibodies inhibited the activity of the respective enzyme. IgG containing antibodies against liver and tumor enzymes inhibited the activity of both enzymes, whereas IgG from sera that did not react with poly(A) polymerase had no effect on either enzyme. These data demonstrated the specificity of these autoantibodies and confirmed the results of the radioimmunoassay.
2827831 Diminished IL-2-induced gamma-interferon production by unstimulated peripheral-blood lymph 1988 Feb A diminished gamma-interferon (IFN-gamma) production by T cells from patients with rheumatoid arthritis (RA) in response to autologous stimulation coincides with a defective regulation of Epstein-Barr virus (EBV) transformation and is in part due to monocyte-produced interleukin-1 (IL-1) inhibitor and prostaglandins. Since IL-2 can act directly on unstimulated T-cells to induce IFN-gamma production we have now examined the effect of recombinant IL-2 (rIL-2) on purified resting T lymphocytes from RA patients. Treatment with rIL-2(25 U/ml) of lymphocytes from 15 controls led to an increased production of 72-h supernatant EBV-inhibitory activity (19 +/- 4% SE without; 48 +/- 7% with rIL-2), but had only minimal or no effect on gamma-interferon production by E-rosetting lymphocytes from 15 patients with active RA. This defect could not be corrected by adding indomethacin to RA cultures.
3141302 Transsynovial kinetics of indoprofen in patients with rheumatoid arthritis and cyclooxygen 1988 Twenty-four patients suffering from rheumatoid arthritis and requiring articular punctures were treated with 200 mg of indoprofen thrice daily for four days. The subjects were divided into four groups each of six patients. Following the last dose, blood and synovial fluid samples were taken simultaneously according to different time schedules. Maximum plasma levels of 17.5 micrograms/ml were observed after 2.5 h. Peak synovial fluid concentrations amounted to 8.1 micrograms/ml 4 h following the last dose. Elimination from synovial fluid occurred at 10.6 h compared to 9.3 h from plasma. Free synovial fluid levels of approximately 50 ng/ml are in the range of concentrations necessary for cyclooxygenase inhibition in mouse peritoneal macrophages.
2884735 [New basic preparations with prolonged action in the treatment of rheumatoid arthritis]. 1987 A long-term comparative study of the classic basic drug-d-Penicillamin and 2 new sulfa drugs: sulfasalazin and salazopyridazin used for the first time in rheumatology, was conducted. Both drugs were shown to produce a "basic" effect in rheumatoid arthritis and to exceed d-Penicillamin in their therapeutic action. Better results were obtained with salazopyridazin. The tolerance to the new antirheumatic sulfa drugs was quite satisfactory; no severe side-effects were noted. Both drugs extend the potentialities of antirheumatoid therapy of prolonged action and warrant further use and study.
3498691 Inhibition of interleukin 2 by serum in healthy individuals and in patients with autoimmun 1987 To study the mechanisms that regulate the activity of interleukin 2 (IL 2) and possibly limit its activity, we have examined normal human serum for its ability to inhibit IL 2-mediated proliferation of a cloned IL 2-dependent cytotoxic T lymphocyte line (CTLL). Normal human serum contains a factor capable of inhibiting IL 2 dependent proliferation of CTLL cells. This factor is absorbed with the cells but not IL 2 molecules. The inhibitor is heat-labile and inactivated by trypsin treatment. The molecular weight of the inhibitor is 70,000-220,000. The imbalance of the inhibitor is observed in serum from patients with autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis. These results suggest that the serum IL 2 inhibitor may play an important role in the in vivo regulatory mechanism of IL 2 activity and in aberrant immune functions in humans.
1830891 Upregulated expression and function of VLA-4 fibronectin receptors on human activated T ce 1991 Aug The VLA-4 (CD49d/CD29) integrin is a cell surface receptor involved in the interaction of lymphoid cells with both extracellular matrix (ECM) and endothelial cells. We have investigated the expression and function of VLA-4 fibronectin (FN) receptors on T cells localized in the inflammed synovium of patients with rheumatoid arthritis (RA). A high proportion of T cells in both synovial membrane (SM) and synovial fluid (SF) expressed the activation antigens AIM (CD69) and gp95/85 (Ea2) as well as an increased number of VLA-4 alpha and beta 1 adhesion molecules, as compared with peripheral blood (PB) T cells from the same patients. Furthermore, the majority of these activated SF T cells were able to adhere to a 38-kD FN proteolytic fragment containing the connecting segment-1 (CS-1) specifically through VLA-4 receptors, whereas a significantly lower proportion of PB T cells displayed this capacity. Therefore, our results show that activated T cells selectively localize at sites of tissue injury in RA disease and provide evidence for the in vivo regulation of the expression and function of the VLA-4 integrin. This regulatory mechanism may enable T cells either to facilitate migration or to persist at sites of inflammation.
2954253 [A new non-steroidal anti-inflammatory drug pirprofen (rengasil) in the treatment of rheum 1987 The results of a double blind clinical study of pirprofen, as compared to piroxicam and placebo in 197 patients with rheumatoid arthritis, as compared to piroxicam in 200 patients with gonarthrosis and/or coxarthrosis, and as compared to naproxen in 165 patients with lumbar spondylosis, are reviewed. In rheumatoid arthritis, pirprofen (1200 mg daily) was significantly superior to placebo, and proved in some respects more active than piroxicam where its daily dose was 20 mg. In patients with osteo-arthrosis affecting major joints and the spine, pirprofen (800 mg daily) showed the same therapeutic effects as piroxicam (20 mg) and naproxen (1000 mg). Owing to its obvious anti-inflammatory effect and good tolerance, pirprofen merits large-scale use in rheumatology.
2914745 Surgical pathology of disease of the mitral valve, with special reference to lesions promo 1989 Feb A consecutive series of 459 mitral valves, which had been surgically excised over a 6-year period, were evaluated by means of macroscopic and histologic study. Of the valves, 379 specimens showed evidence of rheumatic disease (82.6%), 51 were floppy (11.1%), while 29 (6.3%) belonged to a heterogeneous group. The last included cases of ischemic disease (2.4%), infective endocarditis (2.4%), congenital dysplasia (0.9%), rheumatoid arthritis (0.4%), and primary dystrophic calcification (0.2%). Eighty-seven patients had had pure mitral incompetence. Among these, floppiness of the leaflets was the major indication for valvar replacement (58.6%), followed by rheumatic disease (12.7%), ischaemic incompetence (12.7%), and infective endocarditis (11.5%). Particular attention was paid to the clinical-pathological profile of patients with floppy valves as the cause of severe incompetence. This confirmed the prevalence of male patients and the frequent incidence of complications, particularly rupture of tendinous cords (54.9%). A striking difference was also found between the mean age of those patients with and without Marfan's disease (15.3 vs. 53.9 years, P less than 0.001). Although mitral incompetence in the presence of a floppy valve could simply be due to deformity of the leaflets, elongation of the cords and dilatation of the atrioventricular junction, in over half of the cases the precipitating event leading to surgery was rupture of tendinous cords.
2067840 [Ventral approaches to the upper cervical spine]. 1991 Apr The transoral approach to the upper cervical spine and the respective neuraxis has been recognized for almost 100 years, but it is still not in common use. Based on over 200 operations on patients with a variety of lesions and an age range from 2 1/2 to 83 years, we outline the pathological mechanism, surgical anatomy, indications for surgery, preoperative investigations, variations and extensions of the transoral approach to the upper cervical spine, neuraxis and skull base. The most common post-traumatic lesions and the most frequent tumors are discussed and the recommended surgical approach is described. Surgical techniques, possible complications and their management, as well as postoperative care, are listed.
1893073 Regulation of synovial cell proliferation and prostaglandin E2 production by combined acti 1991 May To study the causes of synovitis in rheumatoid arthritis (RA), we have analyzed the effect of several cytokines known to be secreted in RA joints, on synovial cell proliferation and prostaglandin E2 (PGE2) production. Recombinant interleukin-1-beta (IL-1-beta) and tumor necrosis factor-alpha (TNF-alpha) stimulated moderately the DNA synthesis and markedly the production of PGE2. Interferon-gamma (IFN-gamma) was often mitogenic but never induced PGE2 secretion. The association of IL-1-beta and TNF-alpha showed an additive effect on both parameters, whereas addition of IFN-gamma to either monokine reduced the proliferation and increased PGE2 release. Incubation with a crude T cell supernatant or a mixture of cytokines including IL-1-beta, TNF-alpha and IFN-gamma enhanced synovial cell growth and PGE2 production as compared to the effect elicited by each single cytokine. In contrast, interleukin-2 (IL-2) down regulated the synovial cell activation induced by the combined action of the three other cytokines. Taken together, our findings indicate that synovial cell proliferation is weakly stimulated, reaching a two-fold increase over background levels, whatever cytokines are used. Furthermore, proliferation can vary independently of PGE2 production. Nevertheless, the monokines IL-1-beta and TNF-alpha both exert agonistic effects on synovial cell activation, thus contributing to cartilage damage in RA, whereas IFN-gamma, IL-6 or IL-2 may rather play a regulatory role.